A Phase II Study of Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (ViPOR) in Relapsed or Refractory CD10-Negative Diffuse Large B-Cell Lymphoma (DLBCL) and High-Grade B-Cell Lymphoma With MYC and BCL2 Rearrangements (HGBCL-DH-BCL2)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 181
- 主要终点
- Complete response (CR) rate (CD10-negative diffuse large B cell lymphoma [DLBCL] and high grade B-cell lymphoma with MYC and BCL2 with or without BCL6 rearrangements [HGBCL-DH-BCL2])
研究概览
简要总结
This phase II trial tests how well venetoclax, ibrutinib, prednisone, obinutuzumab, and Revlimid® (ViPOR) works in treating patients with CD10 negative diffuse large B-cell lymphoma (DLBCL) and high-grade lymphoma with MYC and BCL2 rearrangements that has come back after a period of improvement (relapsed) and/or that has not responded to previous treatment (refractory). Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Ibrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cell (a type of white blood cells) cancers at abnormal levels. This may help keep cancer cells from growing and spreading. Anti-inflammatory drugs, such as prednisone lower the body's immune response and are used with other drugs in the treatment of some types of cancer. Obinutuzumab, a monoclonal antibody, binds to a protein called CD20, which is found on B cells and some types of leukemia and lymphoma cells. Obinutuzumab may block CD20 and help the immune system kill cancer cells. Revlimid, a type of anti-angiogenesis agent and a type of immunomodulating agent, may help the immune system kill abnormal blood cells or cancer cells. It may also prevent the growth of new blood vessels that cancers need to grow. ViPOR may be an effective treatment option for patients with relapsed and/or refractory CD10 negative DLBCL and high-grade B-cell lymphoma with MYC and BCL2 rearrangements.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the complete response (CR) rate of ViPOR in relapsed/refractory (R/R):
Ia. CD10-negative DLBCL; and Ib. CD10-positive or negative high-grade B-cell lymphoma (HGBCL) with MYC and BCL2 (with or without BCL6) translocations (HGBCL-double hit [DH]-BCL2).
SECONDARY OBJECTIVES:
I. To evaluate the complete response (CR) rate of ViPOR in relapsed/refractory (R/R):
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient must be ≥ 18 years of age
- •Patient must have histologically or cytologically confirmed aggressive B-cell lymphoma as follows:
- •Cohort 1: CD10-negative DLBCL, which includes:
- •CD10-negative non-GCB DLBCL, not otherwise specified (NOS) (i.e., CD10-/BCL6- or CD10-/BCL6+/MUM1+ DLBCL)
- •CD10-negative GCB DLBCL, NOS (i.e., CD10-/BCL6+/MUM1- DLBCL)
- •CD10-negative HGBCL with MYC and BCL6 (without BCL2) translocations (HGBCL-DH-BCL6)
- •CD10-negative HGBCL, NOS (without MYC and BCL2 translocations)
- •CD10-negative T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) OR
- •Cohort 2: CD10-positive or negative HGBCL with MYC and BCL2 rearrangements (with or without BCL6 rearrangement) (HGBCL-DH-BCL2)
- •NOTE: The site principal investigator must review and verify the pathology report findings to ensure the patient is eligible and is assigned to the respective cohort at the time of registration
- •Patient must have relapsed and/or refractory disease after at least 1 prior anthracycline and anti-CD20 antibody-containing regimen
- •Patient must not have confirmed or suspected primary mediastinal large B-cell lymphoma (PMBL)
- •Patient must not be pregnant due to the potential harm to an unborn fetus with the treatment regimens being used.
- •All patients of childbearing potential must have a serum or urine study with a sensitivity of at least 25 mIU/mL within 14 days prior to registration to rule out pregnancy and again within 24 hours prior to starting cycle 1 day 1 of treatment.
- •A patient of childbearing potential is defined as anyone, regardless of whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
- •Patients of childbearing potential must not expect to conceive children by abstaining from sexual intercourse or by using accepted and effective methods of contraception throughout the entire duration of protocol treatment, including during dose interruptions, and for 6 months after the last dose of protocol treatment. Male patients must not father children by abstaining from sexual intercourse or by using a condom during sexual contact with pregnant partners or partners of childbearing potential throughout the entire duration of protocol treatment, including dose interruptions, and for 6 months after the last dose of protocol treatment even if they have had a successful vasectomy
- •Male patients must agree to not donate semen or sperm during the entire duration of protocol treatment or for at least 28 days after the last dose of lenalidomide
- •Patient must agree to abstain from breastfeeding during the entire duration of protocol treatment and for at least 6 months after the last dose of protocol treatment
- •Patient must agree to abstain from donating blood during the entire duration of protocol treatment and for at least 28 days after the last dose of lenalidomide
- •Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
- •Absolute neutrophil count (ANC) ≥ 1,000/mcL without requirement for granulocyte colony stimulating factor (G-CSF) support (obtained ≤ 7 days prior to registration)
- •Hemoglobin ≥ 8 g/dL (obtained ≤ 7 days prior to registration)
- •Platelets ≥ 75,000/mcL without requirement for platelet transfusion support (obtained ≤ 7 days prior to registration)
- •Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (or ≤ 3.0 x institutional ULN for patients with documented Gilberts syndrome) (obtained ≤ 7 days prior to registration)
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 3.0 x institutional ULN (obtained ≤ 7 days prior to registration)
- •Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 30 mL/min/1.73 m^2 (estimated by Cockcroft-Gault method or measured) (obtained ≤ 7 days prior to registration)
- •Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial
- •For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- •Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- •Patient must not have confirmed or suspected primary DLBCL of the central nervous system (CNS) (PCNSL)
- •Patients with history of secondary CNS lymphoma (SCNSL) are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression
- •Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- •Patient must not have taken or require warfarin or other strong CYP3A inhibitors or inducers within 7 days prior to registration.
- •NOTE: Antiplatelet agents, other anticoagulants aside from warfarin, as well as mild or moderate CYP3A inhibitors or inducers are permitted on study but should be used with caution
- •Patient must not have an uncontrolled intercurrent illness that would interfere with the safety or efficacy assessment of this protocol
- •Patient must not have evidence of an active infection at the time of registration
- •Patient must not have the following current or prior anti-cancer treatment:
- •Any chemotherapy, targeted therapy, anti-cancer antibodies, antibody-drug conjugates, or bi-specific antibodies received within 2 weeks prior to registration
- •NOTE: Short courses of corticosteroids or palliative external beam radiation therapy (XRT) prior to registration are permitted
- •More than 3 prior lines of cytotoxic chemotherapy, excluding targeted therapy, anti-cancer antibodies, antibody-drug conjugates, bi-specific antibodies, and radio- or toxin-immunoconjugates
- •NOTE: Cytoreductive chemotherapy followed by autologous stem cell transplant (ASCT) counts as 1 line of cytotoxic therapy. Similarly, cytoreductive chemotherapy (either pre-T-cell collection or as bridging therapy) followed by pre-conditioning therapy/chimeric antigen receptor T-cell (CAR-T) counts as 1 line of therapy, as long as no disease progression occurs between interventions. For both therapies, if progressive disease is documented between 2 distinct regimens, then they should be counted as 2 lines of cytotoxic chemotherapy
- •Radio- or toxin-immunoconjugates within 10 weeks prior to registration
- •Previous treatment with more than one of the following study agents: venetoclax (or another BCL2 inhibitor), ibrutinib (or another BTK inhibitor), or lenalidomide (or another immunomodulatory imide drug [IMiD])
- •Prior autologous stem cell transplant (ASCT), chimeric antigen receptor T-cell (CAR-T) therapy, or allogeneic stem cell (or other organ) transplant within 3 months prior to registration
- •Any evidence of active graft-versus-host disease or requirement for immunosuppressants within 28 days prior to registration
- •NOTE: In addition, patient must have recovered (i.e., ≤ grade 1 or baseline) from all adverse events due to previously administered anti-cancer treatment, surgery, or procedure
- •NOTE: Exceptions to this include events not considered to place the patient at unacceptable risk of participation in the opinion of the treating investigator (i.e., alopecia)
- •Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
- •Patient must have adequate formalin fixed paraffin embedded (FFPE) tumor tissue specimen from the initial diagnostic biopsy or on-study repeat tumor tissue biopsy for molecular analysis
- •NOTE: Excisional tumor biopsy is preferred. Core needle biopsies will be considered adequate if there is enough tissue for the mandatory molecular analysis. Submission of an entire FFPE tumor block is preferred, but if unavailable 10 x 10um FFPE scrolls may be submitted as an alternative. If adequate archived FFPE tumor tissue is unavailable, the patient must be willing to undergo research biopsy for molecular analysis
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排除标准
- 未提供
研究组 & 干预措施
Treatment (ViPOR)
Patients receive venetoclax PO QD on days 2-14, ibrutinib PO QD on days 1-14, prednisone PO QD on days 1-7, obinutuzumab IV on days 1 and 2, and Revlimid PO QD on days 1-14 of each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, PET, CT and/or MRI and optional tumor biopsy and bone marrow aspiration and biopsy throughout the study.
干预措施: Biospecimen Collection (Procedure)
Treatment (ViPOR)
Patients receive venetoclax PO QD on days 2-14, ibrutinib PO QD on days 1-14, prednisone PO QD on days 1-7, obinutuzumab IV on days 1 and 2, and Revlimid PO QD on days 1-14 of each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, PET, CT and/or MRI and optional tumor biopsy and bone marrow aspiration and biopsy throughout the study.
干预措施: Biopsy Procedure (Procedure)
Treatment (ViPOR)
Patients receive venetoclax PO QD on days 2-14, ibrutinib PO QD on days 1-14, prednisone PO QD on days 1-7, obinutuzumab IV on days 1 and 2, and Revlimid PO QD on days 1-14 of each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, PET, CT and/or MRI and optional tumor biopsy and bone marrow aspiration and biopsy throughout the study.
干预措施: Bone Marrow Biopsy (Procedure)
Treatment (ViPOR)
Patients receive venetoclax PO QD on days 2-14, ibrutinib PO QD on days 1-14, prednisone PO QD on days 1-7, obinutuzumab IV on days 1 and 2, and Revlimid PO QD on days 1-14 of each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, PET, CT and/or MRI and optional tumor biopsy and bone marrow aspiration and biopsy throughout the study.
干预措施: Bone Marrow Aspiration (Procedure)
Treatment (ViPOR)
Patients receive venetoclax PO QD on days 2-14, ibrutinib PO QD on days 1-14, prednisone PO QD on days 1-7, obinutuzumab IV on days 1 and 2, and Revlimid PO QD on days 1-14 of each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, PET, CT and/or MRI and optional tumor biopsy and bone marrow aspiration and biopsy throughout the study.
干预措施: Lenalidomide (Drug)
Treatment (ViPOR)
Patients receive venetoclax PO QD on days 2-14, ibrutinib PO QD on days 1-14, prednisone PO QD on days 1-7, obinutuzumab IV on days 1 and 2, and Revlimid PO QD on days 1-14 of each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, PET, CT and/or MRI and optional tumor biopsy and bone marrow aspiration and biopsy throughout the study.
干预措施: Prednisone (Drug)
Treatment (ViPOR)
Patients receive venetoclax PO QD on days 2-14, ibrutinib PO QD on days 1-14, prednisone PO QD on days 1-7, obinutuzumab IV on days 1 and 2, and Revlimid PO QD on days 1-14 of each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, PET, CT and/or MRI and optional tumor biopsy and bone marrow aspiration and biopsy throughout the study.
干预措施: Magnetic Resonance Imaging (Procedure)
Treatment (ViPOR)
Patients receive venetoclax PO QD on days 2-14, ibrutinib PO QD on days 1-14, prednisone PO QD on days 1-7, obinutuzumab IV on days 1 and 2, and Revlimid PO QD on days 1-14 of each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, PET, CT and/or MRI and optional tumor biopsy and bone marrow aspiration and biopsy throughout the study.
干预措施: Positron Emission Tomography (Procedure)
Treatment (ViPOR)
Patients receive venetoclax PO QD on days 2-14, ibrutinib PO QD on days 1-14, prednisone PO QD on days 1-7, obinutuzumab IV on days 1 and 2, and Revlimid PO QD on days 1-14 of each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, PET, CT and/or MRI and optional tumor biopsy and bone marrow aspiration and biopsy throughout the study.
干预措施: Obinutuzumab (Biological)
Treatment (ViPOR)
Patients receive venetoclax PO QD on days 2-14, ibrutinib PO QD on days 1-14, prednisone PO QD on days 1-7, obinutuzumab IV on days 1 and 2, and Revlimid PO QD on days 1-14 of each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, PET, CT and/or MRI and optional tumor biopsy and bone marrow aspiration and biopsy throughout the study.
干预措施: Computed Tomography (Procedure)
Treatment (ViPOR)
Patients receive venetoclax PO QD on days 2-14, ibrutinib PO QD on days 1-14, prednisone PO QD on days 1-7, obinutuzumab IV on days 1 and 2, and Revlimid PO QD on days 1-14 of each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, PET, CT and/or MRI and optional tumor biopsy and bone marrow aspiration and biopsy throughout the study.
干预措施: Ibrutinib (Drug)
Treatment (ViPOR)
Patients receive venetoclax PO QD on days 2-14, ibrutinib PO QD on days 1-14, prednisone PO QD on days 1-7, obinutuzumab IV on days 1 and 2, and Revlimid PO QD on days 1-14 of each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, PET, CT and/or MRI and optional tumor biopsy and bone marrow aspiration and biopsy throughout the study.
干预措施: Venetoclax (Drug)
结局指标
主要结局
Complete response (CR) rate (CD10-negative diffuse large B cell lymphoma [DLBCL] and high grade B-cell lymphoma with MYC and BCL2 with or without BCL6 rearrangements [HGBCL-DH-BCL2])
时间窗: Up to 5 years
Will be assessed using the Lugano Classification and will be defined as the complete disappearance of all detectable clinical evidence of disease, and disease-related symptoms if present prior to therapy.
次要结局
- CR rate (CD10-negative activated B-cell [ABC] and non-ABC DLBCL)(Up to 5 years)
- Overall response rate(Up to 5 years)
- Duration of response (DOR)(From the documented beginning of response to the time of relapse up to 10 years)
- Event-free survival (EFS)(From study entry to any treatment failure including discontinuation of treatment for any reason, such as disease progression, toxicity, patient preference, initiation of new treatment without documented progression, or death up to 10 years)
- Time of progression (TTP)(From study entry until lymphoma progression or death due to lymphoma up to 10 years)
- Progression-free survival (PFS)(From entry onto study until lymphoma progression or death from any cause up to 10 years)
- Overall survival (OS)(From date of study entry to date of death up to 10 years)
- Incidence of adverse events for patients who are CD10-negative ABC DLBCL, and CD10-negative non-ABC (i.e., unclassified or germinal center B-cell) DLBCL, and CD10-positive or negative HGBCL-DH-BCL2(Up to 30 days after last dose of study treatment)
- Event-free survival (EFS)(From study entry to any treatment failure including discontinuation of treatment for any reason, such as disease progression, toxicity, patient preference, initiation of new treatment without documented progression, or death up to 10 years)
- Progression-free survival (PFS)(From entry onto study until lymphoma progression or death from any cause up to 10 years)
- Overall survival (OS)(From date of study entry to date of death up to 10 years)